What lab tests are recommended for a general adult population, particularly those with risk factors such as hypertension, diabetes, or a history of coronary artery disease (CAD), to rule out heart failure?

Outpatient Laboratory Workup to Rule Out Heart Failure

The complete outpatient laboratory workup to rule out heart failure includes: complete blood count, urinalysis, serum electrolytes (including calcium and magnesium), blood urea nitrogen, serum creatinine, fasting blood glucose (or glycohemoglobin), lipid profile, liver function tests, and thyroid-stimulating hormone. 1

Core Laboratory Tests (Class I Recommendation)

The ACC/AHA guidelines mandate the following initial laboratory evaluation for all patients being evaluated for heart failure 1:

Basic Metabolic Panel

• Complete blood count to assess for anemia, which can exacerbate heart failure or mimic its symptoms 1
• Serum electrolytes including sodium, potassium, calcium, and magnesium to identify imbalances that may contribute to or result from heart failure 1
• Blood urea nitrogen and serum creatinine to evaluate renal function, as cardiorenal syndrome is common and affects prognosis 1

Metabolic Assessment

• Fasting blood glucose or glycohemoglobin (HbA1c) to screen for diabetes, a major risk factor for heart failure development 1
• Lipid profile to assess cardiovascular risk and guide treatment of underlying coronary artery disease 1
• Liver function tests to detect hepatic congestion from right-sided heart failure or identify other causes of symptoms 1

Endocrine Screening

• Thyroid-stimulating hormone (TSH) is essential because both hyperthyroidism and hypothyroidism can cause or contribute to heart failure 1

Urinalysis

• Urinalysis to screen for proteinuria (indicating renal disease) and other abnormalities 1

Natriuretic Peptide Testing (Class I for Uncertain Diagnosis)

• BNP or NT-proBNP measurement should be obtained when the clinical diagnosis remains uncertain after initial evaluation, as normal levels make systolic heart failure very unlikely 1, 2
• This test has Level A evidence and is particularly useful in the urgent care or outpatient setting to support or exclude the diagnosis 1
• Elevated levels are sensitive to biological factors including age, sex, weight, and renal function, so interpretation requires clinical context 1

Additional Testing in Selected Patients (Class IIa)

The following tests are reasonable when clinical suspicion exists 1:

Hemochromatosis Screening

• Fasting transferrin saturation to screen for hemochromatosis, especially in patients of Northern European descent, as iron overload can cause reversible cardiomyopathy 1

Infectious Disease Screening

• HIV testing should be considered in high-risk patients, though most HIV-related cardiomyopathy presents after other HIV manifestations are apparent 1

Specialized Testing When Clinically Indicated

• Rheumatologic panel (ANA, rheumatoid factor) if connective tissue disease is suspected 1
• Pheochromocytoma screening (plasma or urine metanephrines) if clinical features suggest this diagnosis 1
• Chagas disease antibodies in patients who have traveled to or immigrated from endemic regions 1

Tests NOT Recommended for Routine Use (Class III)

• Routine measurement of circulating neurohormones (norepinephrine, endothelin) is not recommended 1
• Viral antibody titers have low yield and uncertain therapeutic implications even when positive 1

Essential Non-Laboratory Components

While you asked specifically about laboratory workup, the guidelines emphasize that laboratory tests alone cannot rule out heart failure. The complete evaluation requires 1, 2:

• 12-lead electrocardiogram to assess for arrhythmias, conduction abnormalities, left ventricular hypertrophy, or prior myocardial infarction 1, 2
• Chest radiograph (PA and lateral) to evaluate for cardiomegaly, pulmonary congestion, and pleural effusions 1, 2
• Two-dimensional echocardiography with Doppler as the definitive test to assess left ventricular ejection fraction, chamber size, wall thickness, and valve function 1, 2

Critical Clinical Pearls

Heart failure is highly unlikely if both the chest radiograph and ECG are completely normal, making these essential screening tools even in the outpatient setting 3. However, normal laboratory values do not exclude heart failure with preserved ejection fraction (HFpEF), which accounts for 40-50% of heart failure cases and requires echocardiography for diagnosis 4.

The combination of history, physical examination findings (displaced apex, S3 gallop, elevated jugular venous pressure), and NT-proBNP provides the highest diagnostic accuracy, with NT-proBNP adding the most powerful supplementary diagnostic value beyond clinical assessment 5.